BACE1 inhibitory effects of lavandulyl flavanones from Sophora flavescens

Eun Mi Hwang, Young Bae Ryu, Hoi Young Kim, Dong Gyu Kim, Seong Geun Hong, Jin Hwan Lee, Marcus J. Curtis-Long, Seong Hun Jeong, Jae Yong Park, Ki Hun Park

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

In order to access β-secretase (BACE1), and enzyme strongly implicated in the cause of Alzheimer's disease, inhibitors must possess sufficient lipophilicity to traverse two lipid bilayers. Current drug candidates, which are almost totally peptide-derived, are thus inefficient because cell permeability presents a serious limiting factor. In this study, lipophilic alkylated (C10-C5) flavanones from Sophora flavescens were examined for their inhibitory effects against β-secretase. Lavandulyl flavanones (1, 2, 5, 6, and 8) showed potent β-secretase inhibitory activities with IC50s of 5.2, 3.3, 8.4, 2.6, and 6.7 μM, respectively, while no significant activity was observed in the corresponding hydrated lavandulyl flavanones (4 and 7) and prenylated flavanone (3). As we expected, lavandulyl flavanones reduced Aβ secretion dose-dependently in transfected human embryonic kidney (HEK-293) cells. In kinetic studies, all compounds screened were shown to be noncompetitive inhibitor.

Original languageEnglish
Pages (from-to)6669-6674
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number14
DOIs
Publication statusPublished - 2008 Jul 15
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from the Korea Science and Engineering Foundation (R13-2005-012-02002-0) and the MOST/KOSEF to the Environmental Biotechnology National Core Research Center (R15-2003-012-02001-0). Y.B. Ryu was supported by a scholarship from the BK21 program, the Ministry of Education and Human Resources Development, Korea.

Keywords

  • Alzheimer's disease
  • BACE1
  • HEK 293
  • Lavandulyl flavanone
  • Sophora flavescens

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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